Antibacterial Evaluation and Virtual Screening of New Thiazolyl-Triazole Schiff Bases as Potential DNA-Gyrase Inhibitors.

The global spread of bacterial resistance to drugs used in therapy requires new potent and safe antimicrobial agents. DNA gyrases represent important targets in drug discovery. Schiff bases, thiazole, and triazole derivatives are considered key scaffolds in medicinal chemistry. Fifteen thiazolyl-triazole Schiff bases were evaluated for their antibacterial activity, measuring the growth inhibition zone diameter, the minimum inhibitory concentration (MIC), and the minimum bactericidal concentration (MBC), against Gram-positive (, ) and Gram-negative (, , ) bacteria. The inhibition of and was modest. Compounds , , and showed a similar effect as ciprofloxacin, the antimicrobial reference, against . displayed a better effect. Derivatives , -, , and - expressed MIC values lower than the reference, against . , , and - strongly inhibited the growth of . All compounds were subjected to an in silico screening of the ADMET (absorption, distribution, metabolism, elimination, toxicity) properties. Molecular docking was performed on the gyrA and gyrB from . The virtual screening concluded that thiazolyl-triazole Schiff base is the best candidate, satisfying requirements for both safety and efficacy, being more potent against the bacterial gyrA than ciprofloxacin.